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Information × Registration Number 0225U001643, (0122U001220) , R & D reports Title Synthesis of N,O,S-containing heterocycles and study of their interaction with nucleic acids popup.stage_title Проведення розрахунків біологічної активності синтезованих сполук з нуклеотидами, розробка методів синтезу кластерних сполук ренію та дослідження реакцій отриманих сполук з різними фрагментами РНК Head Okovytyi Serhii І., Доктор хімічних наук Registration Date 04-02-2025 Organization Oles Honchar Dnipro National University popup.description1 Purposeful synthesis of new nucleotide-binding substances (ligands) among N,O,S-heterocyclic compounds and development of principles of their further use in medical practice popup.description2  The result of the reporting stage of the research is quantum chemical modeling of the synthesized compounds for biological targets with nucleotides (aminoacyl-tRNA synthetase, DNA gyrase, polymerase), predictive calculations of physicochemical and pharmacokinetic parameters, acute toxicity and drug-like properties, which made it possible to determine further directions of structural modification of molecules and biological research. It was found that 2-(3-R-1H-[1,2,4]-triazol-5-yl)anilines exhibit high antibacterial activity against St. aureus (MIC 5.2-62. 4 M), 6-substituted 5,6-dihydrotetrazolo[1,5-c]quinazolines - high fungicidal activity against Nakaseomyces glabrata (MIC 0.37-0.47 μМ), exceeding standard drugs (ciprofungin, amphotericin B, caspofungin and micafungin). On the basis of the results of quantum chemical studies, the mechanisms of heterocyclization and nucleophilic cleavage reactions were substantiated, which served as a basis for the synthesis of new heterocycles (2-(3-R-1H-[1,2,4]triazol-5-yl)anilines, substituted 5,6-dihydro[1,2,4]triazino(tetrazolo-)[1,5-c]quinazolines, hydropyrimidinones/thiones/selenones, and others). Quantum chemical modeling was performed for other biological targets (cytochromes, COX-1 and 2, Rab-9A, 50S ribosomal protein L19, sterol 14-alpha-demethylase, etc.), and methods for the synthesis of 2-[((3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)alkyl)thio]–carboxylic acids were developed, 2(3,4)-(2-R-5,6-dihydro[1,2,4]triazolo[1,5-c]–quinazolin-5-yl)benzoic acids, substituted thiourea-containing pteridines, substituted quinonimines/oximes, and compounds with high anti-inflammatory, hepatoprotective and diuretic effects were identified. The analysis of the structure-activity relationship revealed key molecular features that enhance these activities and confirms the prospects for further structural modification of these compounds. Product Description popup.authors Anishchenko Andrii O. Borysenko Iryna O. Haponov Oleksandr O. Dil Kateryna V. Kovalenko Serhii I. Kopteva Svitlana D. Okovytyi Serhii I. Palchykov Vitalii O. Shtemenko Nataliia I. popup.nrat_date 2025-02-04 Close